Brain and Cerebrospinal Fluid α-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in LRRK2-PD.

Background: The neuropathology of Parkinson's disease (PD) associated with leucine-rich repeat kinase 2 (LRRK2) mutations (LRRK2-PD) is heterogeneous and varies with the type of mutation. There are only a few studies evaluating seeding aggregation assays to detect α-synuclein (α-syn) in patients with LRRK2-PD.

Objective: We aimed to investigate whether α-syn real-time quaking induced conversion (RT-QuIC) is a sensitive biomarker of synucleinopathy in LRRK2-PD.

Altered ceramide metabolism is a feature in the extracellular vesicle-mediated spread of alpha-synuclein in Lewy body disorders.

Mutations in glucocerebrosidase (GBA) are the most prevalent genetic risk factor for Lewy body disorders (LBD)-collectively Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies. Despite this genetic association, it remains unclear how GBA mutations increase susceptibility to develop LBD. We investigated relationships between LBD-specific glucocerebrosidase deficits, GBA-related pathways, and α-synuclein levels in brain tissue from LBD and controls, with and without GBA mutations.

Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study.

Background: Isolated rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can be part of the prodromal stage of the α-synucleinopathies Parkinson's disease and dementia with Lewy bodies. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has high sensitivity and specificity for the detection of misfolded α-synuclein in patients with Parkinson's disease and dementia with Lewy bodies. We investigated whether RT-QuIC could detect α-synuclein in the CSF of patients with IRBD and be used as a biomarker of prodromal α-synucleinopathy.

-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson's disease.

Background: Leucine-rich kinase 2 (LRRK2)-linked Parkinson's disease (PD) is clinically indistinguishable from idiopathic PD (IPD). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK2 p.G2019S patients reveal Lewy-type synucleinopathy as its principal histological substrate.

Comparative study of cerebrospinal fluid α-synuclein seeding aggregation assays for diagnosis of Parkinson's disease.

Background: PD diagnosis is based primarily on clinical criteria and can be inaccurate. Biological markers, such as α-synuclein aggregation, that reflect ongoing pathogenic processes may increase diagnosis accuracy and allow disease progression monitoring. Though α-synuclein aggregation assays have been published, reproducibility, standardization, and validation are key challenges for their development as clinical biomarkers.

α-Synuclein real-time quaking-induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism.

A reliable biomarker is needed for accurate and early differentiation between Parkinson disease and the various forms of atypical parkinsonism. We used a novel real-time quaking-induced conversion (RT-QuIC) assay to detect α-synuclein (α-syn) aggregates in cerebrospinal fluid (CSF) of 118 patients with parkinsonism of uncertain clinical etiology and 52 controls. Diagnostic accuracy to distinguish α-synucleinopathies from non-α-synucleinopathies and controls was 84% (sensitivity = 75%, specificity = 94%, area under the curve = 0.

Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies.

We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results.

Cerebrospinal fluid real-time quaking-induced conversion is a robust and reliable test for sporadic creutzfeldt-jakob disease: An international study.

Real-time quaking-induced conversion (RT-QuIC) has been proposed as a sensitive diagnostic test for sporadic Creutzfeldt-Jakob disease; however, before this assay can be introduced into clinical practice, its reliability and reproducibility need to be demonstrated. Two international ring trials were undertaken in which a set of 25 cerebrospinal fluid samples were analyzed by a total of 11 different centers using a range of recombinant prion protein substrates and instrumentation. The results show almost complete concordance between the centers and demonstrate that RT-QuIC is a suitably reliable and robust technique for clinical practice.

Atypical non-progressive pneumonia in goats.

An outbreak of severe respiratory disease in a goat herd was associated with Mycoplasma ovipneumoniae, Mycoplasma arginini, Mannheimia haemolytica and Pasteurella multocida with mortality rates exceeding 20% in kids. Post mortem features in affected kids included severe pleuropneumonia, lung consolidation, large quantities of pleural fluid and pericarditis. This is the first report of atypical proliferative pneumonia in goats in Portugal.